Data show superior efficacy after four weeks of treatment and more rapid onset of action for CBP-201 compared with data from studies of current standard of care therapy for AD
On Day 29, 42.9% and 50.0% of patients receiving CBP-201 300 mg or 150 mg, respectively, achieved "clear/almost clear" skin, defined as a score of 0 or 1 in the IGA score, the endpoint required for FDA approval, compared with 12.5% in the placebo group
SAN DIEGO and TAICANG, China, Jan. 8, 2020 /PRNewswire/ — Connect Biopharma, a clinical-stage biopharmaceutical company aimed at identifying potent and specific immune modulating molecules faster and more efficiently than traditional discovery approaches, today announced positive topline data from the Phase 1b study of its novel IL-4Rα antibody, CBP-201, in patients with moderate-to-severe atopic dermatitis (AD). Results from the study show that CBP-201 has an efficacy profile that is superior to data from clinical studies of the current standard of care therapy for AD after four weeks of treatment, with a favorable safety profile. The company expects to initiate a global Phase 2b clinical study of CBP-201 in patients with moderate-to-severe AD in the first quarter of 2020, which will enroll more than 200 patients and will include up to 90 sites in the United States.
"The results of this Phase 1b trial, while early-stage, demonstrate that CBP-201 provides improvements in all metrics of AD even after only four weeks of treatment," said Mike Royal, MD, Chief Medical Officer of Connect. "We believe the finding that 42.9 percent and 50.0 percent of patients receiving CBP-201 300 mg or 150 mg, respectively, achieved clear/almost clear skin at four weeks is very compelling, especially when compared with data from clinical trials of the current standard of care therapy, in which only 22 to 28 percent of patients on a placebo-adjusted basis achieved this improvement after 16 weeks of treatment. Additional data from the planned Phase 2b study will provide important insight into the role that CBP-201 may play in advancing the care of individuals living with moderate-to-severe AD."
AD, a common condition that can have multiple negative effects on the lives of affected individuals, is a chronic inflammatory disorder characterized by eczematous skin lesions, itch, localized pain, and sleep disturbances. It is also a common condition, occurring in 10-15% of children and 2-4% of adults. Approximately 30% of individuals with AD have moderate-to-severe disease. Patients with moderate-to-severe AD who are not helped by topical corticosteroids continue to have significant unmet needs.
"We are extremely pleased that CBP-201 demonstrated excellent tolerability and rapid onset of efficacy in patients with moderate-to-severe AD after just four weeks of treatment," said Dr. Zheng Wei, co-founder and CEO of Connect Biopharma. "The emerging safety and efficacy profiles of CBP-201 continue to support its best-in-class potential as a treatment option. The potential for dosing every four weeks with CBP-201 compared with every two weeks with the approved biologic therapy, coupled with superior efficacy and a favorable safety profile, would position CBP-201 for both clinical and commercial success. We look forward to confirming these promising Phase 1b results in the Phase 2b study that is expected to begin in the first quarter of 2020."
Key Trial Results
- CBP-201 treatment resulted in rapid improvement in skin lesion as measured by change from baseline in EASI on Day 29.
- 42.9% and 50.0% of patients receiving 300 mg or 150 mg, respectively, achieved "clear/almost clear" skin, defined as a score of 0 or 1 in the Investigator’s Global Assessment (IGA) scores, the primary efficacy endpoint required for FDA approval, compared with 12.5% in the placebo group.
- 100% and 87.5% of patients receiving 300 mg and 150 mg, respectively, achieved at least 50% decrease in Eczema Area and Severity Index (EASI) score (EASI50), compared with 37.5% in the placebo group.
- Mean reductions from baseline in EASI score were 74.4% and 74.0% in the CBP-201 300 mg and 150 mg groups, respectively, compared with 32.9% in the placebo group.
- Mean affected body surface area (BSA) reductions from baseline were 58.7% and 62.7% in the CBP-201 300 mg and 150 mg groups, respectively, compared with 28.7% in the placebo group.
- Skin lesion improvements were evidenced as early as one week after dosing and were correlated with a rapid reduction in pruritus intensity and frequency.
- On Day 15, the average weekly Pruritus Numeric Rating Scale (PNRS) reductions from baseline were 40.4% and 26.4%, for the 300 mg and 150 mg groups, respectively, compared with 3.5% in the placebo group.
- On Day 29, the average weekly PNRS reductions from baseline were 56.4% and 43.6% for the CBP-201 300 mg and 150 mg groups, respectively, compared with 20.6% in the placebo group.
- On Day 29, the weekly average pruritus frequency reductions were 57.1% and 43.0% for the CBP-201 300 mg and 150 mg groups, respectively, compared with 19.9% in the placebo group.
- CBP-201 was well tolerated in this study.
- There were no serious adverse events (SAEs) and no AEs of injection site reaction or conjunctivitis/keratitis in the study.
- The proportion of subjects with at least one treatment emergent adverse event (TEAE) ranged from 62.5% for placebo to 85.7% for the CBP-201 300 mg group. There was no dose-proportional effect on TEAEs either by frequency or severity.
- Most TEAEs were mild in severity, with the majority deemed unrelated to CBP-201.
- There was a single TEAE (atopic dermatitis flare) leading to study treatment discontinuation in one subject in each of the CBP-201 75 mg and placebo groups.
About the Trial
The randomized, double-blind, placebo-controlled, multiple dose escalation study conducted in ten sites in Australia and New Zealand, evaluated the safety and efficacy of CBP-201 after four weeks of treatment in 31 patients with moderate-to-severe AD who have had inadequate response to topical corticosteroids and immunosuppressants. Ten patients in each cohort were randomized 4:1 to CBP-201 (75 mg, 150 mg or 300 mg) or placebo, respectively and were administered study treatment once weekly by subcutaneous injection for four consecutive weeks and followed for an additional seven weeks. The primary endpoints of the study were safety and tolerability of CBP-201, and other endpoints included multiple efficacy assessments (IGA scores, EASI scores, affected BSA and PNRS).
CBP-201 is a potent monoclonal antibody against IL-4Rα, a cell surface protein required for the signaling of both IL-4 and IL-13, which have significant overlapping biological activities and play key roles in inflammatory diseases mediated by type 2 helper T cells (Th2). CBP-201 was discovered internally using Connect Biopharma’s proprietary Immune Modulation Technology Platform and is under clinical development to treat atopic dermatitis and other Th2 inflammatory diseases that have high unmet medical needs. Previously reported results from a Phase 1a clinical study in 48 healthy human study participants showed that CBP-201 was well tolerated and demonstrated rapid and sustained reduction in serum levels of thymus and activation regulated chemokine (TARC, or CCL17), a biomarker for Th2 activity.
About Connect Biopharma
Connect Biopharma is a clinical-stage biopharmaceutical company focused on discovery and development of novel immune modulators for the treatment of autoimmune diseases and inflammation. The company’s proprietary Immune Modulation Technology Platform is a high-throughput screening platform built on the biology of T cell function, and rapidly identifies molecules that target clinically validated disease pathways more efficiently than the traditional discovery approaches.
In addition to CBP-201, the company’s other lead drug candidate is CBP-307, an orally active, next-generation S1P1 and S1P5 modulator for the treatment of a range of autoimmune disorders, including inflammatory bowel disease, psoriasis, and multiple sclerosis. In two completed phase 1 randomized, double-blind, placebo-controlled studies, CBP-307 exhibited an excellent safety profile and potent T cell modulation activity as well as optimal pharmacokinetic and pharmacodynamic profiles, demonstrating best-in-class potential. Two phase 2 studies of CBP-307 are currently underway to evaluate the efficacy and safety of CBP-307 in patients with moderate-to-severe ulcerative colitis and moderate-to-severe Crohn’s disease.
Additional immune modulators in Connect Biopharma’s pipeline include CBP-174, CBP-233, and CBP-312. For more information about the company, please visit www.connectbiopharm.com.
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